Hypersialylation is a feature of pancreatic ductal adenocarcinoma (PDA) and it has been related to tumor malignancy and immune suppression. In this work, we have evaluated the potential of the sialyltransferase inhibitor, Ac53FaxNeu5Ac, to decrease tumor sialoglycans in PDA and to revert its malignant phenotype. Sialoglycans on PDA cells were evaluated by flow cytometry, and the functional impact of Ac53FaxNeu5Ac was assessed using E-selectin adhesion, migration, and invasion assays. PDA tumors were generated in syngeneic mice from KC cells and treated with Ac53FaxNeu5Ac to evaluate tumor growth, mice survival, and its impact on blocking sialic acid (SA) and on the tumor immune component. Ac53FaxNeu5Ac treatment on human PDA cells decreased α2,3-SA and sialyl-Lewisx, which resulted in a reduction in their E-selectin adhesion, and in their migratory and invasive capabilities. Subcutaneous murine tumors treated with Ac53FaxNeu5Ac reduced their volume, their SA expression, and modified their immune component, with an increase in CD8+ T-lymphocytes and NK cells. In conclusion, Ac53FaxNeu5Ac treatment weakened PDA cells' malignant phenotype, thereby reducing tumor growth while favoring anti-tumor immune surveillance. Altogether, these results show the positive impact of reducing SA expression by inhibiting cell sialyltransferases and open the way to use sialyltransferase inhibitors to target this dismal disease.

The aim of the study was to evaluate the dynamic changes of the total Natural Killer (NK) cells and different NK subpopulations according to their differentiated expression of CD16/CD56 in COVID-19 patients. Blood samples with EDTA were analyzed on day 1 (admission moment), day 5, and day 10 for the NK subtypes. At least 30,000 singlets were collected for each sample and white blood cells were gated in CD45/SSC and CD16/CD56 dot plots of fresh human blood. From the lymphocyte singlets, the NK cells subpopulations were analyzed based on the differentiated expression of surface markers and classified as follows: CD16-CD56+/++/CD16+CD56++/CD16+CD56+/CD16++CD56-. By examining the CD56 versus CD16 flow cytometry dot plots, we found four distinct NK sub-populations. These NK subtypes correspond to different NK phenotypes from secretory to cytolytic ones. There was no difference between total NK percentage of different disease forms. However, the total numbers decreased significantly both in survivors and non-survivors. Additionally, for the CD16-CD56+/++ phenotype, we observed different patterns, gradually decreasing in survivors and gradually increasing in those with fatal outcomes. Despite no difference in the proportion of the CD16-CD56++ NK cells in survivors vs. non-survivors, the main cytokine producers gradually decline during the study period in the survival group, underling the importance of adequate IFN production during the early stage of SARS-CoV-2 infection. Persistency in the circulation of CD56++ NK cells may have prognostic value in patients, with a fatal outcome. Total NK cells and the CD16+CD56+ NK subtypes exhibit significant decreasing trends across the moments for both survivors and non-survivors.